Haruyuki Kamiya ^*

• Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Strong repetitive stimulus occasionally enhances the excitability of the axon and leads to the generation of afterdischarge which outlasts the stimulus period originating either from the physiological spike initiation site, mostly at the axon initial segment, or from the ectopic sites for the spike generation. One of the possible mechanisms underlying the stimulus-induced ectopic afterdischarge is the local depolarization due to accumulated potassium ions surrounding the axonal membranes of the distal portion. In this study, the mechanisms were explored by computational approaches using a simple model of hippocampal mossy fibers implemented with the structure of en passant axons as well as experimentally obtained properties of ionic conductances. When slight depolarization of distal axons was given in conjunction with the high-frequency stimulus, robust afterdischarges were triggered after cessation of the repetitive stimulus and lasted for a prolonged period after the stimulus. Each spike during the afterdischarge recorded from distal axons precedes that recorded from the soma, suggesting that afterdischarge was ectopically generated from distal axons and propagated antidromically toward the soma. Notably, when inactivating potassium channels in the model are replaced with non-inactivating ones, repetitive stimuli fail to induce afterdischarge. These results suggested that the inactivating property of axonal potassium channels plays a crucial role in generating the afterdischarge. Accumulated inactivation of potassium channels during strong repetitive stimulation may alter mossy fiber excitability, leading to ectopic afterdischarges from sites distinct from the physiological spike initiation region. axons, it has been suggested that a non-canonical mode called retroaxonal action potentials is triggered from axons distal from the soma in both physiological as well as pathological conditions